The instinct of thirst was a cardinal element in the successful colonization by vertebrates of the dry land of the planet, which began in the Ordovician period about 400 million y ago. It is a commonplace experience in humans that drinking water in response to thirst following fluid loss is a pleasant experience. However, continuing to drink water once thirst has been satiated becomes unpleasant and, eventually, quite aversive. Functional MRI experiments reported here show pleasantness of drinking is associated with activation in the anterior cingulate cortex (Brodmann area 32) and the orbitofrontal cortex. The unpleasantness and aversion of overdrinking is associated with activation in the midcingulate cortex, insula, amygdala, and periaqueductal gray. Drinking activations in the putamen and cerebellum also correlated with the unpleasantness of water, and the motor cortex showed increased activation during overdrinking compared with drinking during thirst. These activations in motor regions may possibly reflect volitional effort to conduct compliant drinking in the face of regulatory mechanisms inhibiting intake. The results suggestive of a specific inhibitory system in the control of drinking are unique.fMRI | swallowing T he colonization of the planetary dry land by vertebrates emerging from the fresh water rivers and swamps over the Ordovician and Silurian period was dependent in major part on the development of the instincts of thirst and sodium appetite.The genetically programmed neural organization determining the behavior embodied in these instincts is protective of the chemical integrity and volume of the circulating milieu intérieur: the extracellular fluids. With thirst, for example, in some manner presently only partly understood, the stimuli provided by sensory input from the dry mouth and desiccated pharynx, increased sodium concentration in the cerebrospinal fluid, the osmotic pressure of the carotid arterial blood, activation of the stretch receptors in the heart, and of the concentration of hormones in arterial blood is centrally integrated to contrive the intensity of the specific subjective state of thirst, and the compulsive intention to acquire water. The intensity of this primordial emotion presumptively determines the quantitative intake during drinking (1, 2).Accurate rapid gratification over 5-10 min of body deficit occurs in species including the camel, burro, sheep, Saharan donkey, goat, cow, dog, or horse depleted of 4-8% of body weight. However, for other species, such as rat, guinea pig, hamster, and for particular consideration human, drinking is much slower. With human, other variables are operative in the gratification process, termed "the consummatory act" (3). When attesting to thirst as a result of experimental dehydration, these species may drink initially more than 50-80% of deficit (4) but then slowly complete intake to repletion. This behavior was termed "voluntary dehydration" by Adolph (5), an early pioneer in this field. Adolph studied man in the desert and was dubious ...